Autonomous Expression of the
 slo
 Gene of the Bicistronic
 nga-slo
 Operon of
 Streptococcus pyogenes

Granert, Carl; Abdalla, Hussein Abdelaziz; Lindquist, Lars; Diab, Asim; Bakhiet, Moiz; Tracey, Kevin J.; Andersson, John

doi:10.1128/iai.70.8.4754.2002

Cited by 4 publications

(5 citation statements)

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“…This regulation is tightly controlled by specific AraC/XylS type regulator-protein ligand interactions under specific environmental conditions (Dasgupta et al, 2004;Ha et al, 2004). The transcription of the nga and slo bicistronic operon is under control of the nga promoter, whereas a weak monocistronic transcription of slo is exerted by a second autonomous promoter that is negatively affected by the SloR regulator (Savic et al, 2002). Now, our microarray data and gel shift assay data showed that MsmR positively regulates the nga/slo transcription by directly binding to the nga promoter region.…”

Section: Discussionmentioning

confidence: 99%

MsmR, a specific positive regulator of the Streptococcus pyogenes FCT pathogenicity region and cytolysin‐mediated translocation system genes

Nakata

Podbielski

Kreikemeyer

2005

Molecular Microbiology

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SummaryAs a prerequisite for colonization or causing local infections, Streptococcus pyogenes (group A streptococci, GAS) need to specifically adhere to eukaryotic cell surfaces. Predominantly responsible adhesin genes are contained in a genotype-specific pattern within the FCT region of the GAS genome. In this study, MsmR, belonging to AraC/XylS type transcriptional regulators, was identified in the FCT region as a positive regulator of the major fibronectin-binding adhesin protein F2 in a serotype M49 strain. Compared with the wild-type strain, the msmR mutant showed reduced binding to immobilized fibronectin and decreased adherence to and internalization into human pharyngeal epithelial cells. These results suggested that altered levels of fibronectin-binding proteins in the mutant affect eukaryotic cell attachment and internalization. Complete transcriptome and reporter fusion assay data revealed that MsmR positively regulates FCT region genes including Nra and cytolysin-mediated translocation system genes. Consistent with the genetic data, the mutant showed attenuated streptolysin O activity and eukaryotic cell cytotoxity. Direct binding of recombinant MsmR to nga , nra/cpa and prtF 2 promoter regions was confirmed by EMSA assays. As prior analysis demonstrated the Nra regulator negatively affects gene expression from the FCT region, MsmR and Nra appear to adversely control crucial virulence factor expression in GAS and thus contribute to a fine-tuned balance between local destructive process and metastatic spreading of the bacteria.

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Section: Discussionmentioning

confidence: 99%

MsmR, a specific positive regulator of the Streptococcus pyogenes FCT pathogenicity region and cytolysin‐mediated translocation system genes

Nakata

Podbielski

Kreikemeyer

2005

Molecular Microbiology

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“…In Clostridium spp., pfoR genes are located upstream of the genes encoding thiol-activated cytotoxins perfringolysin O, tetanolysin O and septicolysin, but PfoR does not seem to regulate toxin expression (Awad and Rood, 2002). In Streptococcus pyogenes, however, the pfoR-like sloR gene was shown to affect streptolysin O expression, despite the fact that these genes are not adjacent in the genome (Savic et al, 2002). These examples clearly demonstrate that comparative sequence analysis is but a first step, rather than a panacea, and has to rely upon and be followed up by experimental studies.…”

Section: Concluding Remarks: Some Unresolved Problemsmentioning

confidence: 99%

Bacterial signal transduction network in a genomic perspective^†

Galperin

2004

Environmental Microbiology

326

315

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SummaryBacterial signalling network includes an array of numerous interacting components that monitor environmental and intracellular parameters and effect cellular response to changes in these parameters. The complexity of bacterial signalling systems makes comparative genome analysis a particularly valuable tool for their studies. Comparative studies revealed certain general trends in the organization of diverse signalling systems. These include (i) modular structure of signalling proteins; (ii) common organization of signalling components with the flow of information from N-terminal sensory domains to the C-terminal transmitter or signal output domains (N-to-C flow); (iii) use of common conserved sensory domains by different membrane receptors; (iv) ability of some organisms to respond to one environmental signal by activating several regulatory circuits; (v) abundance of intracellular signalling proteins, typically consisting of a PAS or GAF sensor domains and various output domains; (vi) importance of secondary messengers, cAMP and cyclic diguanylate; and (vii) crosstalk between components of different signalling pathways. Experimental characterization of the novel domains and domain combinations would be needed for achieving a better understanding of the mechanisms of signalling response and the intracellular hierarchy of different signalling pathways.

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“…Growth rates and hemolytic activities in log and early stationary phase were similar between the two strains ( dicating that inactivation of orf121 has no observable effect on plo expression under these conditions. However, the e¡ects of orf121 may be subtle, as has been observed with pfoR and sloR, putative regulatory genes of CDCs from C. perfringens and Streptococcus pyogenes, respectively [8,24]. To determine the e¡ect of orf121 overexpression on plo production, orf121 was cloned downstream of P lac , on pJGS440.…”

Section: Orf121 Does Not Regulate Plo Expressionmentioning

confidence: 99%

The gene encoding pyolysin, the pore-forming toxin ofArcanobacterium pyogenes, resides within a genomic islet flanked by essential genes

Rudnick

Jost

Songer

et al. 2003

FEMS Microbiology Letters

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The plo gene, encoding the Arcanobacterium pyogenes cholesterol-dependent cytolysin, pyolysin (PLO), was localized to a 2.7-kb genomic islet of reduced %G+C content and alternate codon usage frequency. This islet, conserved among isolates from diverse hosts and geographical locations, separated the housekeeping genes smc and ftsY, which are found adjacent in many prokaryotes. The ftsY and ffh genes, located downstream of the plo islet, encode components of the signal recognition particle. Mutational analysis suggested that these genes were essential for viability in A. pyogenes. The A. pyogenes ffh gene was unable to complement a conditional ffh mutant of Escherichia coli and its overexpression was toxic in E. coli. Mutagenesis of the islet-encoded orf121 did not affect plo expression, indicating that it may not be involved directly in the regulation of plo expression. Regardless, the presence of the plo gene as part of a genomic islet inserted between genes essential for normal growth may provide selective pressure for the retention of this important virulence factor.

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Autonomous Expression of the slo Gene of the Bicistronic nga-slo Operon of Streptococcus pyogenes

Cited by 4 publications

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MsmR, a specific positive regulator of the Streptococcus pyogenes FCT pathogenicity region and cytolysin‐mediated translocation system genes

MsmR, a specific positive regulator of the Streptococcus pyogenes FCT pathogenicity region and cytolysin‐mediated translocation system genes

Bacterial signal transduction network in a genomic perspective^†

The gene encoding pyolysin, the pore-forming toxin ofArcanobacterium pyogenes, resides within a genomic islet flanked by essential genes

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Autonomous Expression of the slo Gene of the Bicistronic nga-slo Operon of Streptococcus pyogenes

Cited by 4 publications

References 0 publications

MsmR, a specific positive regulator of the Streptococcus pyogenes FCT pathogenicity region and cytolysin‐mediated translocation system genes

MsmR, a specific positive regulator of the Streptococcus pyogenes FCT pathogenicity region and cytolysin‐mediated translocation system genes

Bacterial signal transduction network in a genomic perspective†

The gene encoding pyolysin, the pore-forming toxin ofArcanobacterium pyogenes, resides within a genomic islet flanked by essential genes

Contact Info

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Bacterial signal transduction network in a genomic perspective^†